Targeting insulin-like growth factor 1 receptor restricts development and severity of secondary lymphedema in mice

Abstract

Secondary lymphedema is a debilitating chronic tissue swelling in a limb caused by inadequate interstitial fluid drainage due to dysfunctional lymphatic vessels. Pathological enlargement of small lymphatics contributes to lymphatic dysfunction in secondary lymphedema, but molecular mechanisms driving this remodeling are unclear. Here, using a surgical mouse model of secondary lymphedema and whole-genome microarray, we identified the transcript for insulin-like growth factor binding protein 5 (IGFBP5), a negative regulator of insulin-like growth factor (IGF) signaling, as the most profoundly down-regulated in lymphedematous tissue. Notably, IGF signaling via IGF1 receptor (IGF1R) was previous..